Release and metabolism of arachidonic acid in human neutrophils.
Dual radiolabel incorporation of [3H]arachidonic acid and [14C]palmitate or [14C]stearate by human neutrophils was employed to study both the release and metabolism of arachidonic acid. Results indicate the involvement of a phospholipase A2 mechanism causing [3H]arachidonate release from membrane phospholipid. Phosphatidylinositol and phosphatidylcholine were the sources of [3H]arachidonate; about twice as much radiolabeled phosphatidylinositol was degraded as phosphatidylcholine. Challenge of neutrophils with opsonized zymosan and calcium ionophores caused the release of [3H]arachidonate; however, ionophores but not opsonized zymosan led to the production of [3H]hydroxyicosatetraenoic acid and [3H]dihydroxyicosatetraenoic acid. These products were preferentially released by neutrophils into the extracellular milieu in contrast with free [3H]arachidonate which remained cell associated. One-third of the [3H]hydroxyicosatetraenoic acid but not [3H]dihydroxyicosatetraenoic acid was reincorporated into cellular lipid, primarily phospholipid. No significant production of [3H]prostaglandin or [3H]thromboxane was detected. In contrast to zymosan and ionophore, phorbol myristate acetate, another potent stimulant of neutrophil oxidative metabolism and degranulation, did not release [3H]arachidonate.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood*; D000001:Calcimycin / Q000494:pharmacology; D002250:Carbon Radioisotopes; D006801:Humans; D007700:Kinetics; D008055:Lipids / Q000097:blood; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000097:blood; D010743:Phospholipids / Q000097:blood; D014316:Tritium
D001095:Arachidonic Acids; D002250:Carbon Radioisotopes; D008055:Lipids; D010169:Palmitic Acids; D010743:Phospholipids; D014316:Tritium; D016718:Arachidonic Acid; D019308:Palmitic Acid; D000001:Calcimycin